Sandbox Reserved 497: Difference between revisions
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==Mechanism of Action== | ==Mechanism of Action== | ||
A proposed mechanism for the methyl transfer reaction catalyzed by DmdA has recently been published based on the known structural characteristics of DmdA as well as what is known about | A proposed mechanism for the methyl transfer reaction catalyzed by DmdA has recently been published based on the known structural characteristics of DmdA as well as what is known about other reactions, namely redox-neutral methyl transfer reactions involving THF as well reactions that involve a methyl transfer from a sulfonium atom to a nitrogen atom | ||
<ref> Schuller, D.J., Reisch, C.R., Moran, M.A., Whitman, W.B., Lanzilotta, W.N. (2012) Structures of dimethylsulfoniopropinate-dependent demethylase from the marine organism pelagabacter ubique. Protein Sci. 21: 289-298. </ref>. This proposed mechanism, as well as the reasoning behind it, is very similar to the mechanism for S-adenosylmethionine (SAM)-dependent N-methyltransferases. In particular, the proposed mechanism for the methyl transfer reaction catalyzed by DmdA involves an SN2 intermediate with a concerted methyl group and a proton transfer mediated by a water molecule present in the active site. This proposed reaction is logical due to the location of the active site, which is highly acessible by water, as well as the <scene name='Sandbox_Reserved_497/Acidicactivesite/1'>acidic side chains </scene> present in the active site. | <ref> Schuller, D.J., Reisch, C.R., Moran, M.A., Whitman, W.B., Lanzilotta, W.N. (2012) Structures of dimethylsulfoniopropinate-dependent demethylase from the marine organism pelagabacter ubique. Protein Sci. 21: 289-298. </ref>. This proposed mechanism, as well as the reasoning behind it, is very similar to the mechanism for S-adenosylmethionine (SAM)-dependent N-methyltransferases. In particular, the proposed mechanism for the methyl transfer reaction catalyzed by DmdA involves an SN2 intermediate with a concerted methyl group and a proton transfer mediated by a water molecule present in the active site. This proposed reaction is logical due to the location of the active site, which is highly acessible by water, as well as the <scene name='Sandbox_Reserved_497/Acidicactivesite/1'>acidic side chains </scene> present in the active site. Research suggests that the presence of hydrogen bonds involving acidic residues polarizes the substrate thus lowering the enrgy barrier of the reaction and facilitating the mechanism for (SAM)-dependent N-methyltransferases and the homologous proposed mechanism for the DmdA enzymatic reaction. Further support for the proposed mechanism for the reaction catalyzed by DmdA is provided by the presence of a sulfonium atom in DMSP, the substrate for DmdA, since the presence of this atom tends to make methyl a fairly good leaving group. Finally this proposed mechanism is also supported by the presence of specific structurally significant amino acids in DmdA, some of which were discussed above, as they facilitate hydrogen bonding, ring stacking, and other key interactions that make DmdA structurally similar to other proteins GcvT family but enzymatic ally similar to (SAM)-dependent N-methyltransferases. | ||
[[Image:DmdA_Mechanism.jpg|thumb|500px|right|The proposed mechanism for the methyl transfer reaction catalyzed by DmdA. This image was obtained directly from Schuller et al.]] | [[Image:DmdA_Mechanism.jpg|thumb|500px|right|The proposed mechanism for the methyl transfer reaction catalyzed by DmdA. This image was obtained directly from Schuller et al.]] | ||